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Compositions for inferring bovine traits

a technology of compositions and traits, applied in the field of gene association analysis, can solve the problems of inability to visualize the carcass of beef, low accuracy, and no cost effective methods for identifying live cattle that give accurate prediction, and achieve the effect of maximizing individual potential performance, superior genetic potential for desirable characteristics, and maximizing the value of edible mea

Inactive Publication Date: 2005-11-24
CARGILL INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0023] The present invention provides methods, systems, and compositions that allow the identification and selection of cattle with superior genetic potential for desirable characteristics. Accordingly, the present invention provides methods, compositions, and systems for managing, selecting and mating, breeding, and cloning cattle. These methods for identification and monitoring of key characteristics of individual animals and management of individual animals maximize their individual potential performance and edible meat value. The methods of the invention provide systems to collect, record and store such data by individual animal identification so that it is usable to improve future animals bred by the producer and managed by the feedlot. The methods, compositions, and systems provided herein utilize information regarding genetic diversity among cattle, particularly single nucleotide polymorphisms (SNPs), and the effect of nucleotide occurrences of SNPs on important traits.
[0025] This invention allows the identification of animals that have superior traits that can be used to identify parents of the next generation through selection. These methods can be imposed at the nucleus or elite breeding level where the improved traits would, through time, flow to the entire population of animals, or could be implemented at the multiplier or foundation parent level to sort parents into most genetically desirable. The optimum male and female parent can then be identified to maximize the genetic components of dominance and epistasis, thus maximizing heterosis and hybrid vigor in the market animals.

Problems solved by technology

However, the visual appraisal of a beef carcass cannot occur until the animal is harvested.
Ultrasound can be used to give an indication of marbling prior to slaughter, but accuracy is low if ultrasound is done at a time significantly prior to harvest.
Currently there are no cost effective methods for identifying live cattle that give accurate prediction of the genetic potential to produce beef that is well-marbled.
Currently there are no procedures for identifying live animals whose beef, if cooked properly, would be tender.
Neither of these procedures can be used to any practical effect in a fabrication setting as the need to age product prior to testing would lead to maintenance of inventory of fabricated product that would be cost prohibitive.
It has been difficult for the livestock industry to combine genetics for red meat yield and marbling and / or tenderness.
In fact, conventional measurement techniques indicate that marbling and red meat yield tend to be antagonistic.
Currently, cattle producers do not have tools to identify animals with superior genetic potential for rapid growth prior to purchase.
In addition, there are no methods currently available to identify animals which combine capability for superior growth rate with desirable carcass characteristics.
While many methods of measurement and selection of cattle in feedlots have been tried, both visual and automated, such as ultrasound, none have been successful in accomplishing the desired end result.
Yet to date, it has been unable to devise a system or method to accomplish on a large scale what is needed to manage the current diversity of cattle (i.e. least about 100 different breeds and co-mingled breeds) to improve the beef product quality and uniformity fast enough to remain competitive in the race for the consumer dollar spent on meat.
While the classical breeding approach has produced steady genetic improvement in livestock species it is limited by the fact that accurate prediction of an individual's genetic potential can only be achieved when the animal reaches adulthood (fertility and production traits) or is harvested (meat quality traits).
This is particularly problematic for meat animals since harvested animals obviously cannot enter the breeding pool.
Furthermore, it is difficult to utilize the classical breeding approach for traits that are difficult (disease resistance) or costly (meat tenderness) to measure.
Limited success has been achieved for each of these methods in identifying genes that contribute to genetic variation for defined traits.
However, each method also has limitations, as the primary objectives of the molecular breeding approach described above have not been achieved.
However, this approach does have limitations and is analogous to finding a needle-in-the-haystack.
With over 30,000 genes characterized in humans and mouse as a result of the whole genome sequence the first difficulty is identifying a gene that will actually contribute to genetic variation for a specific trait.
Secondly, a large enough set of individuals must be sequenced to find the sequence variant that is responsible for or at least highly associated with the effect.
While it is feasible to meet all of these conditions to discover significant associations the cost of this approach is high because it is a random method that cannot be targeted to genes that have the largest effect.
Differential gene expression has been effective in identifying genes that are turned on or off by extreme differences in environment or by disease, but has been less successful in identifying genes that contribute to phenotypic variation in livestock production traits.
Differential gene expression technology has been successfully used to elucidate biochemical pathways and to understand basic cellular functions but has not demonstrated any utility in the development of diagnostic assays to predict genetic potential of animals for specific traits.
Even if differential expression of a gene is observed and can be directly attributed to phenotypic variation for a trait there is no guarantee that a sequence variant can be found in the gene or that the sequence variant is responsible for the effect.
Although the within family QTL linkage approach has resulted in a number of reported linkages between targeted traits and specific marker locations this approach does not result in the direct development of diagnostic assays that can predict an animals genetic potential for the targeted trait.
In practice, the research populations used for these experiments are very small, often only representing two or three different sire families, and as such, they do not represent the broad pattern of genetic variation that is observed across commercial animal populations.
These small research populations are also problematic because the QTL can only be identified when it is heterozygous for a particular family group.
Furthermore, research populations designed to identify linkages in livestock species are usually half-sib designs where it is only possible to measure the genetic variation contributed by the male side of the pedigree.
Half-sib designs have limited effectiveness in discovering significant linkages because only one-half of the genetic variation is accounted for in the analysis.
These extreme phenotypic crosses do not represent mainstream industry breeding practices and therefore, any reported linkage is suspect because it may only exist as an artifact within the research population and may not actually be segregating in commercial animal breeding populations.
Another limitation of the within family QTL approach is the lack of marker density for the linkage map used in the study.
Due to cost and genotyping throughput issues all reported QTL linkage studies performed to date in livestock species have only used 100 to 200 total markers to cover the entire genome.
With such a limited number of markers it is impossible to pinpoint the exact location of the QTL on the chromosome.
Because of these large distances, recombination between homologous chromosomes does not allow the use of linked markers identified in research populations to be used as predictors of genetic potential in commercial animal populations.
In summary, three different experimental approaches have been used with limited success to identify genes, chromosomal regions or DNA markers that account for a large proportion of the genetic variation observed in economically important traits in livestock species.
The results achieved from research programs utilizing these methods have not been widely utilized to date because they do not account for enough of the total genetic variation to allow accurate prediction of an animal's performance for a specific trait.
Furthermore, even when successful these approaches are only capable of identifying additive genetic components while ignoring non-additive genetic components such as dominance (i.e. dominating trait of an allele of one gene over an allele of a another gene) and epistasis (i.e. interaction between genes at different loci) which are critical to the development of diagnostics that can be utilized by animal breeders to accurately predict genetic potential for economically important traits in livestock species.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Generation of a High-Density Bovine Genetic SNP Map

[0194] This example illustrates the generation of a high density bovine genetic SNP map created through a whole genome sequencing of the bovine genome using the shotgun sequencing approach. This approach was selected to provide hundreds of thousands of SNP markers, as described by Venter, J. C, et al., (Science 291:1304-1351 (2001), in order to perform a whole-genome association study with adequate density of markers to ensure discovery of markers in disequilibrium with mutations influencing the targeted traits.

[0195] Shotgun sequencing was performed with four different bovine individuals that represented different breed types. The shotgun sequencing was performed according to the methods of Venter, J. C, et al., (Science 291:1304-1351(2001)). By this method, random fragments of bovine sequence were generated and size selected to 2.5 and 10 kb. These fragments of bovine DNA were inserted into a sequencing vector to create high qua...

example 2

Identification of Bovine SNPs Associated with Tenderness, Fat, Marbling, Yield, and / or Daily Gain

[0197] This example illustrates the identification of SNPs from the high-density bovine, SNP map identified in Example 1, that are associated with the traits meat tenderness, fat thickness, marbling, yield, and / or daily gain.

[0198] DNA samples from bovine subjects were obtained by collecting 50 ml of whole blood from the 4,791 bovine subjects. 25 ml of whole blood was used for DNA extraction using standard methods and concentrations of DNA were calculated using standard fluorimetric methods. Animals representing less than or equal to the 10th percentile of low numeric phenotypic animals (44 individuals) and the 90th percentile and greater of high phenotypic animals (44 individuals) were identified for each trait. The low numeric values were identified as “Low” and the high numeric values were identified as “High”. DNA samples were pooled from bovine individuals that represent high and ...

example 3

Determination of the Distance of Disequilibrium in Cattle

[0201] This example utilizes a few of the associated SNPs disclosed in Example 2, to identify additional SNPs that are associated with the same traits, using the physical proximity on the genome of the SNPs. Furthermore, the results are used to calculate a distance of disequilibrium in cattle. In this example, “shear force” is used to refer to tenderness, “vision retail yield” is used to refer to retail yield, and “average daily gain” is used to refer to daily gain.

[0202] In the past 10 years numerous methods have been developed to identify alleles associated with phenotypic effects, traits or diseases. Linkage disequilibrium and measures of linkage disequilibrium have been of particular interest for studies of complex traits or diseases (see reviews L. R. Cardon and J. I. Bell, “Association study Designs for Complex Diseases”, Nature Reviews / Genetics 2:91-99 (2001); N. A. Rosenberg and M. Nordborg “Genealogical Trees, Coale...

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Abstract

Methods, compositions, and systems are provided for managing bovine subjects in order to maximize their individual potential performance and edible meat value, and to maximize profits obtained in marketing the bovine subjects. The methods and systems draw an inference of a trait of a bovine subject by determining the nucleotide occurrence of at least one bovine SNP that is identified herein as being associated with the trait. The inference is used in methods of the present invention to establish the economic value of a bovine subject, to improve profits related to selling beef from a bovine subject; to manage bovine subjects, to sort bovine subjects; to improve the genetics of a bovine population by selecting and breeding of bovine subjects, to clone a bovine subject with a specific trait, to track meat or another commercial product of a bovine subject; and to diagnose a health condition of a bovine subject. Methods are also disclosed for identifying additional SNPs associated with a trait, by using the associated SNPs identified herein.

Description

CROSS REFERENCE TO RELATED APPLICATION [0001] This application claims the benefit of priority under 35 U.S.C. § 119(e) of U.S. Ser. No. 60 / 437,482, filed Dec. 31, 2002, the entire content of which is incorporated herein by reference.BACKGROUND OF THE INVENTION FIELD OF THE INVENTION [0002] The invention relates generally to gene association analyses and more specifically to polymorphisms and associated traits of bovine species. BACKGROUND INFORMATION [0003] Under the current standards established by the United States Department of Agriculture (USDA), beef from bulls, steers, and heifers is classified into eight different quality grades. Beginning with the highest and continuing to the lowest, the eight quality grades are prime, choice, select, standard, commercial, utility, cutter and canner. The characteristics which are used to classify beef include age, color, texture, firmness, and marbling, a term which is used to describe the relative amount of intramuscular fat of the beef. W...

Claims

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Application Information

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IPC IPC(8): C07H21/04
CPCC12Q1/6876C12Q1/6888C12Q2600/156C12Q1/6881C12Q1/6827Y02A90/10C12Q1/6883C12Q2600/124C12Q2600/16C12Q2600/172
Inventor DENISE, SUEKERR, RICHARDROSENFELD, DAVIDHOLM, TOMBATES, STEPHENFANTIN, DENNIS
Owner CARGILL INC
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